VentriGel goes into pigs

Researchers at the University of California, San Diego and Ventrix Inc.
have developed a catheter-compatible hydrogel that restored cardiac function in
a pig model with myocardial infarction.1 Ventrix is now scaling up
manufacture of the hydrogel, called VentriGel,
and hopes to take it into clinical trials by year end.

In prior work, UCSD and Ventrix developed a hydrogel
scaffold derived from porcine cardiac extracellular matrix (ECM) and showed
that injecting it into rat hearts improved cardiac repair and function.2,3
The hydrogel was designed to mimic the mammalian heart's native ECM, which is
important for proper cardiac function but is lost in the infarct region after a
heart attack.

Now, the researchers have evaluated the same scaffold in
a pig model of myocardial infarction (MI), which more accurately reflects human
cardiac physiology.

In pigs, catheter-mediated delivery of VentriGel at two
weeks post-MI increased cardiac function and decreased pathological left
ventricular remodeling compared with delivery of saline control or no
injection. Histology studies showed that VentriGel also increased cardiac
muscle tissue and decreased fibrosis in the infarct region compared with
controls.

A series of safety and biocompatibility studies showed
that catheter-delivered VentriGel did not adversely affect peripheral tissues
or cause arrhythmias in the pigs, nor did the hydrogel scaffold induce an
immune rejection response or spontaneous formation of thromboemboli in rats.
Finally, in human blood samples, the hydrogel did not affect coagulation.

Results were published in Science Translational
Medicine. Ventrix cofounder Karen Christman, the corresponding author and
an assistant professor of bioengineering at UCSD, led the research team.

"The current study is significant because it
increases our confidence that our technology is working the way we think it is,"
said Ventrix CMO Paul Chamberlin. "The hydrogel scaffold improved wall
motion in the heart, attenuated remodeling and didn't cause arrhythmias in the
pig model. This work gives additional preclinical validation of our hypothesis
that VentriGel, given post-MI, will help improve cardiac function."

Chamberlin added that VentriGel could be delivered to
the heart using a minimally invasive catheter system, whereas most other
injectable biomaterials being developed for cardiac repair need to be delivered
via needle syringe, which would require an invasive surgical procedure.

"In many cases, other off-the-shelf injectable
biomaterials are not capable of being delivered to the heart with a cardiac
catheter," added Ventrix CEO and cofounder Adam Kinsey, a coauthor on the
paper.

Progressing into patients

Ventrix's initial
clinical plans are to develop the hydrogel scaffold in the EU. The company is
scaling up GMP manufacturing of clinical-grade VentriGel and expects to start a
trial by year end.

Chamberlin said the company initially plans to evaluate
catheter-mediated delivery of VentriGel in patients with a recent MI event but
thinks the product also could be applied to patients who are further removed
from the MI event.

"Our early clinical plans will be to develop our
product to treat patients in the acute MI scenario. Generally speaking, we want
to initially target patients who have Class I or II heart failure, but we think
the use of our product could eventually be expanded to the broader heart
failure population as well," he said.

According to New York Heart Association guidelines,
patients with Class I heart failure have cardiac disease but show no limitations
in physical activity, whereas those with Class II heart failure show slight
limitations such as fatigue, palpitations, dyspnea or angina resulting from
normal physical activity.

Another possible scenario for VentriGel is in patients
already undergoing surgery to restore cardiac function, said Harald Ott, a
fellow in cardiothoracic surgery at the Massachusetts General Hospital
and instructor in surgery at Harvard Medical School.
"Patients undergoing a ventricular restoration procedure may achieve
additional benefit from an injection of this hydrogel scaffold."

Moving forward, "it will be important to know how
the ECM hydrogel treatment and revascularization either by percutaneous
coronary intervention or bypass grafting could be used in conjunction with one
another," said Jun Liao, assistant professor of biomedical engineering at Mississippi State University.
"It would also be interesting to know how treatment with this ECM hydrogel
would affect standard pharmacological therapies such as b-blockers and ACE
[angiotensin-converting
enzyme] inhibitors."

Ott suggested that the researchers may want to look into
how other implantable, porcine-derived products were developed, as this could
provide insights on how to further assess the biocompatibility and potential
immunogenicity of the hydrogel scaffold.

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